220769-83-5Relevant articles and documents
Tuning spin-crossover transition temperatures in non-symmetrical homoleptic meridional/facial [Fe(didentate)3]2+complexes: what for and who cares about it?
Deorukhkar, Neel,Besnard, Céline,Guénée, Laure,Piguet, Claude
, p. 1206 - 1223 (2021/02/09)
The [FeN6] chromophores found in [Fe(didentate)3]2+complexes, where didentate is a non-symmetrical 2-(6-membered-heterocyclic ring)-benzimidazole ligand (Lk), exist as mixtures of two geometricalmer(C1-symmetry) andfac(C3-symmetry) isomers. Specific alkyl-substituted six-membered heterocyclic rings connected to the benzimidazole unit (pyridines in ligandsL1-L3, pyrazines inL4-L5and pyrimidines inL6-L7) control the ligand field strength and the electron delocalization so that [FeII(Lk)3]2+display tunable thermally-induced spin transitions in solution. Thermodynamic, spectroscopic (UV-Vis, NMR) and magnetic studies in solution demonstrate that [Fe(L6)3]2+(L6= 1-methyl-2-(pyrimidin-2-yl)-1H-benzo[d]imidazole) exhibits a close to room temperature spin transition (T1/2= 273(3) K) combined with a high stability formation constant n acetonitrile), which makes this complex suitable for the potential modulation of lanthanide-based luminescence in polymetallic helicates. A novel method is proposed for assigning specific thermodynamic spin crossover parameters tofac-[Fe(L6)3]2+andmer-[Fe(L6)3]2+isomers in solution. The observed difference relies mainly on the entropic content ΔSmerSCO? ΔSfacSCO= 11(1) J mol?1K?1, which favors the spin transition for the meridional isomer. Intermolecular interactions occurring in the crystalline state largely overcome minor thermodynamic trends operating in diluted solutions and a single configurational isomer is usually observed in the solid state. Among the thirteen solved crystal structures1-13containing the [M(Lk)3]2+cations (M = Fe, Ni, Zn,Lk=L6-L7), pure meridional isomers are observed six times, pure facial isomers also six times and a mixture (44%merand 56%fac) is detected only once. Solid-state magnetic data recorded for the FeIIcomplexes show the operation of slightly cooperative spin transitions in7(fac-[Fe(L6)3]2+) and12(mer-[Fe(L7)3]2+). For the meridional isomer in6, a two-step spin state transition curve, associated with two phase transitions, is detected.
Synthesis of N-trifluoromethyl amides from carboxylic acids
Flavell, Robert R.,Liu, Jianbo,Parker, Matthew F. L.,Toste, F. Dean,Wang, Sinan,Wilson, David M.
supporting information, p. 2245 - 2255 (2021/08/12)
Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.
SPIROCYCLE COMPOUNDS AND METHODS OF MAKING AND USING SAME
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Paragraph 00225, (2019/03/17)
Provided herein are compounds and compositions useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.
Copper-Catalyzed Electrochemical C-H Amination of Arenes with Secondary Amines
Yang, Qi-Liang,Wang, Xiang-Yang,Lu, Jia-Yan,Zhang, Li-Pu,Fang, Ping,Mei, Tian-Sheng
supporting information, p. 11487 - 11494 (2018/09/13)
Electrochemical oxidation represents an environmentally friendly solution to conventional methods that require caustic stoichiometric chemical oxidants. However, C-H functionalizations merging transition-metal catalysis and electrochemical techniques are, to date, largely confined to the use of precious metals and divided cells. Herein, we report the first examples of copper-catalyzed electrochemical C-H aminations of arenes at room temperature using undivided electrochemical cells, thereby providing a practical solution for the construction of arylamines. The use of n-Bu4NI as a redox mediator is crucial for this transformation. On the basis of mechanistic studies including kinetic profiles, isotope effects, cyclic voltammetric analyses, and radical inhibition experiments, the reaction appears to proceed via a single-electron-transfer (SET) process, and a high valent Cu(III) species is likely involved. These findings provide a new avenue for transition-metal-catalyzed electrochemical C-H functionalization reactions using redox mediators.
MULTISUBSTITUTED AROMATIC COMPOUNDS AS INHIBITORS OF THROMBIN
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Paragraph 0380-0381, (2017/12/07)
There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of thrombin, which compounds include substituted pyrazolyl or substituted triazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing a disease or disorder, which disease or disorder is amenable to treatment or prevention by the inhibition of thrombin.
Electron-deficient heteroarenium salts: An organocatalytic tool for activation of hydrogen peroxide in oxidations
?turala, Ji?í,Bohá?ová, Soňa,Chudoba, Josef,Metelková, Radka,Cibulka, Radek
, p. 2676 - 2699 (2015/03/18)
A series of monosubstituted pyrimidinium and pyrazinium triflates and 3,5-disubstituted pyridinium triflates were prepared and tested as simple catalysts of oxidations with hydrogen peroxide, using sulfoxidation as a model reaction. Their catalytic efficiency strongly depends on the type of substituent and is remarkable for derivatives with an electron-withdrawing group, showing reactivity comparable to that of flavinium salts which are the prominent organocatalysts for oxygenations. Because of their high stability and good accessibility, 4-(trifluoromethyl)pyrimidinium and 3,5-dinitropyridinium triflates are the catalysts of choice and were shown to catalyze oxidation of aliphatic and aromatic sulfides to sulfoxides, giving quantitative conversions, high preparative yields and excellent chemoselectivity. The high efficiency of electron-poor heteroarenium salts is rationalized by their ability to readily form adducts with nucleophiles, as documented by low pKR+ values (pKR+ red > -0.5 V). Hydrogen peroxide adducts formed in situ during catalytic oxidation act as substrate oxidizing agents. The Gibbs free energies of oxygen transfer from these heterocyclic hydroperoxides to thioanisole, obtained by calculations at the B3LYP/6-311++g(d,p) level, showed that they are much stronger oxidizing agents than alkyl hydroperoxides and in some cases are almost comparable to derivatives of flavin hydroperoxide acting as oxidizing agents in monooxygenases.
MULTISUBSTITUTED AROMATIC COMPOUNDS AS SERINE PROTEASE INHIBITORS
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Paragraph 0254; 0255, (2014/09/29)
There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of kallikrein, which compounds include substituted pyrazolyl or substituted triazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which disease or disorder is amenable to treatment or prevention by the inhibition of kallikrein.
Novel tetrahydropyrido[1,2-a]isoindolone derivatives (valmerins): Potent cyclin-dependent kinase/glycogen synthase kinase 3 inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts
Boulahjar, Rajaa,Ouach, Aziz,Matteo, Chiurato,Bourg, Stephane,Ravache, Myriam,Guével, Rémy Le,Marionneau, Séverine,Oullier, Thibauld,Lozach, Olivier,Meijer, Laurent,Guguen-Guillouzo, Christiane,Lazar, Sa?d,Akssira, Mohamed,Troin, Yves,Guillaumet, Gérald,Routier, Sylvain
, p. 9589 - 9606 (2013/01/16)
The development of CDK and GSK3 inhibitors has been regarded as a potential therapeutic approach, and a substantial number of diverse structures have been reported to inhibit CDKs and GSK-3β in recent years. Only a few molecules have gone through or are currently undergoing clinical trials as CDK and GSK inhibitors. In this paper, we prepared valmerins, a new family containing the tetrahydropyrido[1,2-a]isoindone core. The fused heterocycle was prepared with a straightforward synthesis that was functionalized by a (het)arylurea. Twelve valmerins inhibited the CDK5 and GSK3 with an IC50 100 nM. A semiquantitative kinase scoring was realized, and a cellular screening was done. At the end of our study, we investigated the in vivo potency of one valmerin. Mice exhibited good tolerance to our lead, which proved its efficacy and clearly blocked tumor growth. Valmerins appear also as good candidates for further development as anticancer agents.
SGC STIMULATORS
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Page/Page column 101; 102, (2011/10/10)
Compounds of Formula I are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.
